In the past 10 years it has become established that collagenase released by rheumatoid synovial tissue contributes heavily to joint destruction in patients with rheumatoid arthritis. Having studied the enzyme itself and factors which might affect its action in vivo (e.g., temperature, the genetic type of collagen substrate, cross-linking among collagen molecules) we have turned our attention to study of the manner in which rheumatoid synovial collagenase is secreted from cells, its behavior and characteristics as a latent enzyme, and the mechanisms of its activation in vivo. Studies involve isolated, adherent cells dissociated enzymatically from fresh rheumatoid synovium and plated in cell culture. Additional studies will involve determination of both collagen synthesis and degradation in scleroderma. Previous studies have involved only one or the other; but if it is to be accepted that collagen accummulation in tissues is a function of both synthesis and degradation, both factors must be examined in the same tissues. BIBLIOGRAPHIC REFERENCES: Harris, E.D., Jr.: Recent insights into the pathogenesis of the proliferative lesion in rheumatoid arthritis. Arthritis Rheum. 19: 68, 1976. Miller, E.J., Harris, E.D., Jr., Chung, E., Finch, J.E., McCroskery, P.A., and Butler, W.T.: Cleavage of type II and III collagens with mammalian collagenase: Site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. Biochemistry 15: 787-792, 1976.